Periodontal disease has been recently identified as a risk factor for increased morbidity and mortality for systemic diseases such as pancreatic cancer, cardiovascular disease (atherosclerosis, myocardial infarction, and stroke), and diabetes, as well as for pregnancy complications such as preterm birth. It is well established that periodontal disease results from microorganisms in dental plaque biofilm. Inflammatory reactions initiated by oral bacteria and their components are implicated locally in the pathogenesis of periodontal tissue destruction, and may contribute to the development of systemic disease. While causality has yet to be confirmed, some studies have shown that oral health interventions may impact biological markers of inflammation and disease. The goal of this project is to develop a prescription antimicrobial oral rinse to reduce bacterial bioburden in the oral cavity and combat oral disease and inflammation. Current oral rinse products are either fraught with side effects such as staining and taste alterations that limit their usage to acute settings, or are ineffective. Based on preliminary studies, the oral rinse developed herein is expected to be more effective than currently available prescription products without the side effects. The development of a highly effective oral rinse may have the potential to have a profound impact on public health and achieve significant commercial success. This study is a Fast-Track proposal that combines both Phase I and Phase II studies in one application. The Phase I portion has two Specific Aims: Aim 1. Compound Oral Rinse Formulations for Use in Clinical Trials Aim 2. Evaluate Dose-Response of the Oral Rinse in a Human Clinical Trial of Gingival Inflammation and Investigate Effects on Biological Markers Indicative of Systemic Disease. The Phase II portion has three Specific Aims: Aim 1. Compound Oral Rinse Formulations for Use in Clinical Trials Aim 2. Evaluate the Oral Rinse in a Human Clinical Trial of Gingivitis to Satisfy FDA Requirements and Investigate Effects on Biological Markers Indicative of Systemic Disease.